Glyceryl monooctanoate, and excellent solvent for cholesterol in vitro, has recently been shown to dissolve human cholesterol gallstones when infused into the common bile duct for several days-weeks. The physical chemical nature of the interaction between cholesterol and monoglycerides leading to high solubility, however, has not been investigted. Possible mechanisms include simple solvation (dielectric constant effect), hydrogen-bonding, interaction of the hydrocarbon chains with cholesterol, and self-association or micellization. Preliminary studies indicate that cholesterol solubility in these systems can be substantially increased by optimization of fatty acid chain lenght, water and electrolyte content of the solution. Gastrointestinal side effects have been reported with glyceryl monooctanoate infusion although the incidence is unclear at present. The shorter perfusion times requried suing solvent systems with increased cholesterol solubility should result inreduced incidence of side effects. A physical chemical approach is proposed to determine the mechanism of interaction of cholesterol with monoglycerides and the effects of added non-toxic substances on cholesterol solubility. These studies will lead to development of improved solvent systems for dissolution of uman cholesterol gallstones.